Evaluation of apoptosis-associated protein (Bcl-2, Bax, cleaved caspase-3 and p53) expression in canine mammary tumors: An immunohistochemical and prognostic study

Abstract

Apoptosis is an important process involved in pathogenesis and progression of neoplasia. However, it has been not so far extensively investigated in canine mammary tumors (CMTs). Therefore the aim of our study was to determine Bcl-2, Bax, cleaved caspase-3 (CC3) and p53 expression in CMTs and evaluate their correlation with host/tumor factors, and overall survival (OS). Bcl-2 expression was often found in benign lesions and in patients with low TNM stage. Expression of Bax, CC3 and p53 was observed in malignant CMTs. The expression of apoptosis-associated proteins was not significantly associated with OS. A positive-p53 status was significantly related with poorer tumor differentiation, higher mitotic index (MI), more invasive growth, necrosis, and occurred often in CMTs from large breed dogs. In the shorter-survival group of dogs (≤18months), a positive correlation was found between CC3 and Bcl-2 expression; CC3 and MI, ERα and p53 expression, while in the longer-survival group (>18months) CC3 expression was negatively correlated with ERα, whereas p53 expression was positively correlated with MI. We confirmed the usefulness of such parameters as: tumor size, MI, type of growth, tumor metastasis and TNM stage in predicting OS in a univariate analysis. In multivariate analysis we identified age as an independent prognostic factor for OS. Expression of single apoptosis-associated protein should not be used as a prognostic marker. However, we showed significant correlation patterns of expression of proteins involved in apoptotic-signaling pathways in shorter- and longer survival groups. So far, there have been only a few similar reports published.